This invention relates to a composition for use as a specific immune enhancing factor in therapy for vaccination as well as production of antibodies for harvesting. The composition of the invention is capable of potentiating in vivo the specific antibody response to antigens having low immunogenicity. The composition may be delivered in solution with a pharmacologically acceptable solvent.
Antigens are defined as any substance which is foreign to a living organism and which, on coming into contact with the immune system thereof, activate a complex mechanism of cellular interactions which tend to eliminate the antigen and restore the previous equilibrium. Antigen as the term is used herein shall include proteins, lipids, DNA or carbohydrates. Characteristic features of an antigen are the capacity to induce production of specific antibodies (immunogenicity) which are capable of selectively binding to it (antigenicity) and inactivating it. Some antigens, however, have low immunogenicity and stimulate an antibody response in vivo which is insufficient to give effective immunity to the organism, or to provide sufficient antibodies for harvesting and preparation of polyclonal and monoclonal antibodies. The immune response to an antigen which is administered to a host can be enhanced by the use of adjuvants. An adjuvant is any substance which nonspecifically enhances the immune response to an antigen.
The immune response is mediated by a variety of cells in the immune system. There are two types of immune response: humoral immunity mediated by antibodies, (specific immunity) and cellular immunity mediated primarily by cytotoxic T-lymphocytes. Antigen presenting cells possess and present antigen to both B and T cells. The B cell secretes specific antibodies as a result of activation and T cells (either helper cells to the humoral response or cytotoxic T-cells) respond. Adjuvants have been shown to augment both immune responses. Initial presentation of an antigen induces both IgM and IgG antibodies forming the primary response. This production of antibodies may fall off, however, over time. A secondary response which principally involves the production of IgG antibodies may be triggered by the secondary or later-in-time presentation of the antigen. This generation of a specific immune response generally takes a second inoculation of antigen or even a series of inoculations over several weeks. This is so for even highly immunogenic proteins and additional problems are encountered with less immunogenic compounds. A secondary or even primary response, however, is not guaranteed merely by priming the host with an antigen.
The immunogenicity of an antigen can be improved if it is administered together with adjuvants such as killed bacteria or immunologically inert substances which are capable of increasing the concentration of the antigens presented to the immune system. Adjuvants enhance the immune system response when administered with an antigen, producing higher antibody titers and prolonged host response. The most commonly used adjuvant is Freund's adjuvant. Incomplete Freund's adjuvant comprises a water and oil emulsion and Freund's complete adjuvant which comprises the above with the addition of Microbacterium tuberculosis and alum. Freund's adjuvant, however, has several disadvantages in that it often causes acute pain and may cause the host to develop lesions at the site of injection.
Another commercially available adjuvant with wide use is monophosphoryl lipid A (MLP)/trehalose dicorynomycolate (TDM) (Ribi Immunochem. Research, Inc., Hamilton, Mont.). Alum and aluminum hydroxide have also been used as an alternative to Freund's adjuvant, however, these also present problems in view of inefficiency toward synthetic antigens and thymus independent antigens. Further, numerous adjuvants of bacterial or chemical origin have been proposed in the prior art but few are both highly efficient and free from side effects and none have been found to enhance only specific immunity.
It is therefore an object of the present invention to provide a factor which specifically enhances the immune response to a particular antigen creating a high antibody titer, and reducing time course for production of antibody.
Yet another object of the present invention is to provide a hapten which can be adducted to any carrier and cause it to become immunogenic.
It is yet another object of the present invention to provide a factor with high fluorescence which can be used for labeling and detecting presence of antibodies or other complex biomolecules in any of a number of available immunochemical techniques.
Other objects of the invention will become dear from the detailed description of the invention which follows.